I imagine it can be done, but you're looking at several potential issues, technical and logistical.
1. That many cards are just not going to fit in one box. That's probably the biggest issue you're going to run into. That and trying to shuffle those massive piles. (Also, 1500+ is a drastic underestimation. If I recall correctly, each set is around 1200 cards, so you're looking more in the range of 3500+)
2. You're going to lose a lot of flavor. Whatever set you're playing gets a lot of its feel from the cards that are present or absent. You may, for example, go through an entire adventure of S&S without encountering a single pirate. Granted, you still get the flavor of the scenarios and locations, but you risk a lot of weird circumstances
3. Some characters really struggle outside their home deck. The poster child for this is Lirianne, who will really struggle to encounter enough guns to see her deck upgrade appropriately throughout the Adventure Path.
4. The balance of the game changed between RotR and S&S, and I think there was a bit more of a change going into WotR. (Essentially, the difficulty curve in RotR was Logarithmic, which turned out caused the middle adventures to be way underpowered compared to the average character at that point. In S&S they changed to a more linear curve, so difficulty is much more consistent. WotR will probably be tweaking individual elements, and I think the coefficient on the increase by AD went down slightly, based on comparing Mike's advice for homebrew cards from June vs now) That means that you risk much larger difficulty shifts between scenarios depending on how much luck you have.
I believe those are the biggest issues to trying something like this. If you think you can deal with those issues, then go nuts! Hope it's tons of fun. Personally, I'm too intimidated by the thought of the Monster deck around AD 3 to try it myself.
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Absolutely you can do this.
I guess the question is what are you trying to do? Mix the boons and banes together to just create more variety? Just to see what happens?
Are you going to be playing with the newer WotR characters?
While RotR boons and banes didn't have a lot of theme to them compared to S&S, S&S obviously had more aquatic, pirate and swashbuckling to it's cards. So when you're mixing that stuff in and trying to play the new WotR characters, you'll be diluting more than enhancing. WotR characters are geared towards the cards from that set. If you're playing S&S character in WotR, then mixing in S&S cards will help those characters but as for banes, they won't fit in well with WotR.
Also, you had the mechanics with S&S with ships and structural damage. That won't be there with WotR. And we're not sure what's being introduced in WotR that might hamper RotR stuff.
As I just finished work on an adventure that blends Skull & Shackles and Rise of the Runelords, I think I can take a shot at this.
Yes, you can combine two box sets together, it just takes more admin time. The characters created for each boxset and their expansion pack characters are intended to be used for that boxset.
Jirelle and Lirianne don't really work so well in Rise of the Runelords, as their powers are very ship and firearm specific. The same would be true with characters who have an emphasis on Craft checks, since ROTR doesn't offer as much bang for your buck in potions and ship repair.
I tried to combine the two worlds, so that characters from both ends could find themselves useful at varying times. It does increase the challenge of the game overall.
You will find, in combining sets, that it is a pain to run more than one game out of a box, since the cards will end up in different places and can be irritating to track down. Furthermore, character sheets might get a little messy since players will be writing in cards from sets not intended for them, though you have this problem when adding Character Class Deck cards to a non-OP home game as well.
I imagine Wrath of the Righteous will pose similar problems for players who want to combine boons from different decks.
I think as the game ages, the homebrew scene will concoct more custom adventures that combine different locations and encourages some more grand strategizing. I enjoyed playing my adventure from both boxes, it's like the world gets twice as big all the sudden. It's fun. :)